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Pharmacol Biochem Behav. 2006 Sep;85(1):170-7. Epub 2006 Sep 6.

Effect of the 5-HT(6) serotonin antagonist MS-245 on the actions of (-)nicotine.

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Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298-0540, USA.


The 5-HT(6) serotonin receptor antagonist MS-245 neither substitutes for nor antagonizes the discriminative stimulus effects of (-)nicotine. However, MS-245 was shown to enhance the potency of (-)nicotine in Sprague-Dawley rats trained to discriminate 0.6 mg/kg of (-)nicotine from saline vehicle in a typical two-lever drug discrimination paradigm such that a combination of MS-245 (5.0 mg/kg) plus the ED(50) dose of (-)nicotine caused the animals to respond as if they had received the training dose of (-)nicotine. MS-245 also potentiated the hypolocomotor actions, but not the antinociceptive effects, of (-)nicotine in mice. The results suggest possible involvement of serotonin-regulated signaling mechanisms in certain behavioral effects of nicotine.

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